Familial Hypercholesterolemia: Challenges for a High-Risk Population: JACC Focus Seminar 1/3.

The availability of statins, ezetimibe, and PCSK9 inhibitors has significantly improved the prognosis of familial hypercholesterolemia (FH). However, a great number of individuals with FH do not achieve guideline-recommended low-density lipoprotein (LDL) cholesterol levels despite maximal lipid-lowering therapy. Novel therapies that lower LDL independent of LDL receptor activity can help mitigate atherosclerotic cardiovascular disease risk in most homozygous FH and many heterozygous FH patients. However, access to novel therapies remains limited for heterozygous FH patients with persistent elevation of LDL cholesterol despite treatment with multiple classes of cholesterol-lowering therapies. Conduction of cardiovascular outcomes clinical trials in patients with FH can be challenging because of difficulty in recruitment and long periods of follow-up. In the future, the use of validated surrogate measures of atherosclerosis may allow for clinical trials with fewer study participants and shorter duration, thereby expediting access to novel treatments for patients with FH.
Competing Interests: Funding Support and Author Disclosures Dr Malick is supported by a training grant from the New York Academy of Medicine. Dr Koenig has received consulting fees and lecture fees from AstraZeneca, Novartis, and Amgen; has received consulting fees from Pfizer, The Medicines Company, DalCor Pharmaceuticals, Kowa, Corvidia Therapeutics, OMEICOS, Novo Nordisk, Esperion, LIB Therapeutics, New Amsterdam Pharma, TenSixteen Bio, Genentech, and Daiichi-Sankyo; has received lecture fees from Berlin-Chemie, Bristol Myers Squibb, and Sanofi; and has received grant support and provision of reagents from Singulex, Abbott, Roche Diagnostics, and Dr Beckmann Pharma. Dr Rader is a consultant for Alnylam, Novartis, Pfizer, and Verve; and is chief scientific advisor and current chair of the Board of Directors for the Family Heart Foundation. Dr Rosenson has received research funding to his institution from Amgen, Arrowhead, Lilly, Novartis, and Regeneron; has received consulting fees from Amgen, Arrowhead, CRISPR Therapeutics, Lilly, Lipigon, Novartis, Precision Biosciences, and Verve; has received honoraria from nonpromotional educational activities from Amgen and Kowa; has received royalties from Wolters Kluwer; has stock holdings in MediMergent, LLC; and has pending patents on analytical methods and systems for biocellular marker and detection using microfluidic profiling (PCT/US2019/026364) and compositions and methods relating to the identification and treatment of immunothrombotic conditions (PCT/US2020/63104926), and quantification of Lp(a) vs non-Lp(a) ApoB concentration novel validated equation (PCT/US2021/63248837). Dr Choi has reported that he has no relationships relevant to the contents of this paper to disclose.
(Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)